Fever, Rash, and Lung Crackles in a 25-Year-Old Woman

Jansen Tiongson, MD; John Sakles, MD; Harvey W. Meislin, MD


August 13, 2020


Toxic shock syndrome (TSS) is mediated by enterotoxins produced by Staphylococcus aureus or Streptococcus pyogenes. TSS became prevalent in the early 1980s (for S aureus) and 1993 (for S pyogenes). Staphylococcal TSS was first described in 1978, when seven children presented to an emergency department with acute-onset fever, vomiting, diarrhea, and sore throat; they subsequently went into septic shock and multiorgan dysfunction.[1]

In the early 1980s, the incidence of staphylococcal TSS among healthy, young, menstruating women increased owing to a specific manufacturing defect in tampons. The tampons neutralized the acidic vaginal environment during menstruation, thus increasing oxygen tension and raising carbon dioxide levels in the vagina, providing a medium for S aureus growth. Once this was discovered, tampon manufacturing was changed, and the incidence of S aureus TSS declined from 12 cases per 100,000 population in 1980 to 1 case per 100,000 population in 1986. The incidence as of 1996 is 0.5 case per 100,000 population.[2,3]

Group A streptococcal TSS was not well described until 1993, when children with varicella presented 2-4 weeks later with a clinical syndrome highly suggestive of staphylococcal TSS. The incidence rate in 1999 was 4.3-5.5 cases per 100,000 population, with a mortality rate of about 5%-10% in children and 30%-80% in adults.[3]

In 1993, the following consensus definition for streptococcal TSS was created[4]:

  • Isolation of group A Streptococcus from a normally sterile site (ie, blood, cerebrospinal fluid, pleural fluid, or peritoneal fluid)

  • Hypotension

  • 2 or more of the following:

    • Renal impairment (creatinine concentration > 2 mg/dL, or twice the baseline value for a patient with renal disease)

    • Coagulopathy

    • Elevated liver enzyme values

    • ARDS

    • Erythematous macular rash

    • Soft-tissue necrosis

The pathophysiologic connection between varicella and streptococcal TSS has yet to be determined, but the increased use of the vaccine substantially decreased the incidence of TSS, from 27% during the prevaccination period in 1993-1995 to 2% in 1999-2001. As a result, Stevens and colleagues[2] postulated a link between the manifestation of the herpes zoster virus and TSS. The actual correlation between the 2 entities has yet to be fully deciphered.

Nonsteroidal anti-inflammatory drug (NSAID) use has also been shown to be a risk factor for both types of TSS. Chuang and colleagues[3] described a 1992 study in the United Kingdom showing that 92% of patients with TSS had previous NSAID use. NSAIDs are believed to foster TSS development because they impair granulocyte function while enhancing the production of cytokines. Also, NSAIDs may mask disease progression and delay diagnosis by relieving pain, reducing swelling, and suppressing fever.[3]


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